Brain Research Bulletin (Jul 2024)
SOCS modulates JAK-STAT pathway as a novel target to mediate the occurrence of neuroinflammation: Molecular details and treatment options
Abstract
SOCS (Suppressor of Cytokine Signalling) proteins are intracellular negative regulators that primarily modulate and inhibit cytokine-mediated signal transduction, playing a crucial role in immune homeostasis and related inflammatory diseases. SOCS act as inhibitors by regulating the Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway, thereby intervening in the pathogenesis of inflammation and autoimmune diseases. Recent studies have also demonstrated their involvement in central immunity and neuroinflammation, showing a dual functionality. However, the specific mechanisms of SOCS in the central nervous system remain unclear. This review thoroughly elucidates the specific mechanisms linking the SOCS-JAK-STAT pathway with the inflammatory manifestations of neurodegenerative diseases. Based on this, it proposes the theory that SOCS proteins can regulate the JAK-STAT pathway and inhibit the occurrence of neuroinflammation. Additionally, this review explores in detail the current therapeutic landscape and potential of targeting SOCS in the brain via the JAK-STAT pathway for neuroinflammation, offering insights into potential targets for the treatment of neurodegenerative diseases.